SUMMARY Multiple studies using different methodologies have found that compared to non-Hispanic whites (NHWs), Hispanic women who are survivors of breast cancer are more likely to report impairments in health-related quality of life (hr-QOL) attributable to emotional functioning (increased depression and distress), physical functioning (fatigue), and social functioning. This increased survivorship burden or the combination of different hr-QOL domains has been found to exist even when controlling for cancer treatment factors. Evidence suggests that socioeconomic factors, socio-cultural factors, and inflammation may be involved in the survivorship burden. With respect to the latter, the PI and others have shown that inflammation is associated with the severity of depression and fatigue in NHW breast cancer survivors. Stress-based theories of health suggest that in addition to socioeconomic factors, socio-cultural factors are also important for understanding the survivorship burden. These include acculturation and acculturation stress, social status, stigmatization, social support, and familism. Low acculturation has been associated with poor emotional functioning in Hispanic breast cancer survivors. Interestingly, acculturation stress has also been linked to increased inflammation in other racial groups, suggesting that stress related to socio-cultural factors may impact the biology of hr-QOL impairments in Hispanic breast cancer survivors. Connections between stress and inflammation involved with the survivorship burden have been studied using short-term psychological stress challenges in the laboratory. Specifically, exaggerated inflammation responsiveness to short-term laboratory stress has been found in individuals of low socioeconomic status, suggesting that stress in the laboratory may reveal unique aspects of the pathophysiology of hr-QOL impairments not otherwise apparent at rest. The PI and others have used similar procedures (the Trier Social Stress Test [TSST]), to reveal increased inflammation in individuals with depression. The overarching goal of this proposal is to determine if hr- QOL impairments experienced by Hispanic breast cancer survivors are associated with stress- associated inflammation in a manner that involves socio-cultural factors. Accordingly, the current proposal features two specific aims. First, the study will work to determine if inflammation in response to short- term psychological stress challenge in the laboratory with the TSST predicts hr-QOL disparities experienced by Hispanic compared to non-Hispanic white breast cancer survivors. And second, the study will explore the relationships among stress-related inflammation and socio-cultural factors to predict hr-QOL disparities experienced by Hispanic breast cancer survivors. Accomplishment of these aims will provide critical insight into the likely stress pathophysiological mechanisms of inflammation and socio-cultural factors involved in the survivorship burden experienced by Hispanic breast cancer survivors, and may eventually result in novel risk screening strategies and interventions for this important and underserved group.